Effect of liposome and cyclodextrin entrapment on retardation of glutathione decomposition of nitroimidazolyl sulfones.
A new class of radiosensitizing pharmaceuticals derived from 4-nitro-5-imidazolyl sulfones has its clinical potential compromised by a metabolic reaction with plasma glutathione which leads to a much less active metabolite. Entrapment of two members of the class in three different liposomes, one polymerized liposome, and a beta-cyclodextrin system has shown that this glutathione condensation can be suppressed by a rate factor of nearly 50-fold. Stabilizations of these metabolically labile radiosensitizers appear to relate to their lipid-buffer partition coefficients and to the fluidity of the liposome membrane in which they are entrapped.
Heindel
N D
ND
Institute for Health Sciences, Lehigh University, Bethlehem, PA 18015.
Egolf
R A
RA
Stefely
J S
JS
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003505:Cyclodextrins / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D006207:Half-Life; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*; D009593:Nitroimidazoles / Q000737:chemistry*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013450:Sulfones / Q000737:chemistry*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D008081:Liposomes; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D013450:Sulfones; D047392:beta-Cyclodextrins; C067146:1-methyl-4-nitro-5-imidazolyl-4-iodophenyl sulfone; C067145:1-methyl-4-nitro-5-imidazolyl-2-chloro-6-methylphenyl sulfone; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D005978:Glutathione